Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.3 (
collagenase
)
18,340
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Signal transduction events in monocyte matrix metalloproteinase (MMP) production have been shown to include a PGE(2)-cAMP-dependent step. To determine earlier pathway components, we examined the role of mitogen-activated protein kinases (MAPKs) in the regulation of monocyte
MMP-1
and MMP-9, two major MMPs induced by LPS. Stimulation with LPS resulted in the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) and mitogen-activated kinase p38. The p38-specific inhibitor SB203580 suppressed p38 activity and
MMP-1
mRNA and protein, but increased ERK activity and MMP-9 mRNA and protein. In contrast, the MAPK kinase 1/2-specific inhibitor PD98059 inhibited
MMP-1
and MMP-9. However, both MAPK inhibitors decreased the production of cyclooxygenase-2 and PGE(2), but only the inhibition of
MMP-1
by SB203580 was reversed by PGE(2) or dibutyryl cAMP. Examination of the effect of these MAPK inhibitors on the promoters of
MMP-1
and MMP-9 revealed that PD98059 inhibited the binding of transcription factors to all of the MMP promoter-specific complementary oligonucleotides tested. However, SB203580 only inhibited the binding of
MMP-1
-specific CREB and
SP 1
oligonucleotides, which was reversed by PGE(2). Additionally, SB203580 enhanced transcription factor binding to the oligonucleotides complementary to a NF-kappaB site in the promoter of MMP-9. Thus, LPS induction of
MMP-1
production by monocytes is regulated by both ERK1/2 and p38, whereas MMP-9 stimulation occurred mainly through the ERK1/2 pathway. Moreover, p38 regulates
MMP-1
mainly through a PGE(2)-dependent pathway, whereas ERK1/2-mediated
MMP-1
and MMP-9 production involves the activation of additional MMP promoter sites through a PGE(2)-independent mechanism.
...
PMID:Differential regulation of lipopolysaccharide-induced monocyte matrix metalloproteinase (MMP)-1 and MMP-9 by p38 and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases. 1279 56
